Coordination of DNA Replication and Histone Synthesis During S Phase

  • Johanna PaikEmail author
  • Serena Giovinazzi
  • Akash Gunjan


The coordination of DNA replication with histone synthesis is of utmost importance as any imbalance between the two processes results in genomic instability and may even cause lethality. Hence, to maintain genome stability, histone synthesis is regulated at multiple levels—transcriptionally, posttranscriptionally and by modulating protein stability. This tight regulation facilitates the creation of a very transient histone pool for replication-coupled chromatin assembly and ensures that histone synthesis is downregulated when DNA replication is completed or stalled due to replication inhibition. As illustrated in this chapter, the bulk of histone synthesis during S phase is activated by the same cell cycle signals that initiate DNA replication and downregulated by the same DNA damage response pathways that arrest the DNA replication machinery upon DNA damage. Conversely, the availability of histone proteins and their chaperones that help package the newly replicated DNA into chromatin in turn regulate replication fork progression. Further, in senescent cells, the histone chaperone Histone Regulatory Homolog A (HIRA), a co-repressor of histone gene transcription, plays an important role in the formation of transcriptionally silent heterochromatin that incorporates replication-dependent histone genes as well as many genes needed for DNA replication to concomitantly shut down both histone and DNA synthesis. This chapter discusses the current state of knowledge on the coregulation of histone and DNA synthesis during S phase.


Histone Histone gene regulation Chromatin assembly Histone chaperone Replication-dependent histones MCM HIRA Cyclin Cdk NPAT SLBP DDR SAHF Hir 


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, College of MedicineFlorida State UniversityTallahasseeUSA

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